The Role of Comprehensive Genomic Profiling in Colorectal Cancer

March is Colorectal Cancer (CRC) Awareness Month, and while CRC is an important topic of conversation year-round, this is an especially critical time to reflect on how scientific research and advancements in personalized medicine are transforming the outlook for people living with this disease.

CRC is the third most common type of cancer diagnosed in both men and women in the United States and the third leading cause of cancer-related deaths.¹ One thing that’s particularly intriguing for researchers is that, in recent years, there has been a significant rise in CRC among younger people. A new report from the American Cancer Society highlights that half of new colon and rectal cancer diagnoses are now in people age 66 and younger. And the number of CRC cases diagnosed in individuals younger than 50 increased from 6% in 1990 to 11% in 2013.² What’s been commonly known as a disease impacting older adults is now becoming more and more prevalent in younger patients. This shift has led researchers to look deeper at how the drivers of cancer differ across various age groups and how these differences may inform treatment decisions. As we collaboratively push forward to better understand the evolution of this disease, and ultimately improve patient outcomes, I wanted to take a moment to reflect on some important strides we’ve made along the way:

THE VALUE OF COMPREHENSIVE GENOMIC PROFILING

KRAS mutations are the most frequent known driver alterations in colorectal tumors—about 30-50% of CRC patients have tumors harboring these mutations.³ And while these mutations are important for understanding tumor growth and aggressiveness, having a KRAS mutation also indicates that these patients are unlikely to respond to anti-EGFR therapy. Following from these foundational observations around KRAS in CRC, significant efforts have been made to find additional clinically relevant biomarkers that might help inform treatment decisions.

For example, a prior Foundation Medicine study of over 4,000 colorectal cancers looked at other recurrent alterations aside from KRAS mutations that could be indicative of response or resistance to certain targeted therapies, such as approved anti-EGFR therapies. These included other RAS pathway alterations beyond KRAS, as well as PI3K pathway and receptor tyrosine kinase alterations. These findings underscore how important it is that CRC patients’ tumor samples are tested with comprehensive genomic profiling (CGP), verses single gene or hot spot testing, to help identify potentially relevant alterations. While there is more research to be done in this area, this study is an important step forward in providing valuable insight into the drivers of CRC and the potential of CGP to guide treatment decisions, including the option of immunotherapy.

AGE RELATED DIFFERENCES IN CRC

Further, as we discover more about the genomic drivers of CRC, we are learning how these drivers can differ based on the age of the patient—an area of particular interest given the rise in incidence rates of CRC among younger people. Another Foundation Medicine study conducted late last year found that TP53 and CTNNB1 alterations were more common in younger patients (under 40 years), while KRAS, BRAF, and FAM123B were more commonly altered in older patients (40+ years). Additional research will be conducted to determine whether the differences in genomic profiles can inform personalized therapeutic strategies for younger patients with early-onset CRC. This data reinforces that regardless of age, it is important for CRC patients to receive CGP so that more potentially relevant alterations can be uncovered.

THE FUTURE FOR CRC PATIENTS

We’ve made incredible progress in CRC research, but there is more to be done to inform and enable access to precision medicine options for more patients. As we learn more about the biology of cancer, we are finding that the age-related differences in cancer drivers can be extremely important when it comes to finding the right treatment option. Our CEO, Cindy Perettie, touched on this recently. She wrote about a study presented at the San Antonio Breast Cancer Symposium, which found that younger women with advanced breast cancer had lower frequencies of PIK3CA alterations, yet higher frequencies of BRCA1 and BRCA2, compared to older women. These studies demonstrate that each person’s cancer is truly unique, though looking at commonalities across age groups might begin to provide valuable insight into treatment options and response. For now, given the complex nature of CRC, making comprehensive genomic profiling a standard of care could a good place to start.